Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for +publisher:"Penn State University" +contributor:("Teresa Wood, Committee Chair/Co-Chair"). Showing records 1 – 2 of 2 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


Penn State University

1. Rowzee, Anne Marie. EXPRESSION AND FUNCTION OF INSULIN-LIKE GROWTH FACTOR SIGNALING RECEPTORS IN MAMMARY EPITHELIAL CELL GROWTH .

Degree: 2008, Penn State University

The ultimate function of the mammary gland is to nourish newborns to sustain mammalian life post-partum. Development and differentiation of the mammary gland occurs postnatally under the control of a complex system of hormonal and environmental cues making the mammary gland an important model of study for both developmental biology and endocrinology. Furthermore, breast cancer is the “number one cause of cancer death in Hispanic women” and the “second most common cause of cancer death in white, black, Asian/Pacific Islander and American Indian/Alaska Native women” according to the Centers for Disease Control and Prevention. These statistics make it clear that ongoing research in both breast cancer and normal mammary gland development is imperative to women’s health. The primary cause of breast cancer is transformation of mammary epithelial cells (MECs) that result in unregulated cell proliferation and subsequent mammary carcinomas. Several components of the insulin-like growth factor (IGF) system, the IGF ligands and the IGF-type I receptor (IGF-1R) in particular, regulate both normal and transformed MEC growth. Previous studies from our laboratory examined expression of the IGF ligands and the IGF-1R in normal mammary gland development and demonstrated that the IGF ligands and the IGF-1R are expressed in distinct patterns during normal development. Subsequent analysis of receptor affinity for IGF ligands demonstrated that the insulin receptor isoform A (IR-A) is an IGF-II-sensitive signaling receptor and furthermore, that hybrid receptors consisting of equal parts IGF-1R and insulin receptor (IR), preferentially bind IGF ligands. Herein, we have developed and tested a quantitative PCR assay to accurately measure IGF-1R, IR-A and IR isoform-B (IR-B) expression on the same scale. We have used this assay to quantify mRNA expression of IGF sensitive receptors in primary MECs during mammary gland development. These data demonstrate that IR isoforms are expressed at much higher levels than the IGF-1R at all times. Subsequent protein analysis demonstrated that due to this disproportion, at least 49% of IGF-1R is present as part of a hybrid receptor during pregnancy stages. We next provide preliminary data that demonstrate preferential activation of the IGF-1R rather than hybrid receptors by IGF-I in vivo. Furthermore, we demonstrate that insulin stimulates IGF-1R activation in vivo, either by stimulating classic IGF-1R or IGF-1R present in a hybrid receptor. The importance of IGF-1R signaling in MEC development is further supported by microarray analysis of a MEC-specific conditional deletion of the IGF-1R during post-pubertal development. These data suggest a functional role for IGF-1R signaling via the PI3K/Akt pathway in regulating expression of cell cycle regulatory molecules. In the final section of this thesis, we present in vitro data that support the findings of the microarray analysis and demonstrate that activation of the PI3K/Akt/mammalian target of rapamycin pathway stimulates cell cycle… Advisors/Committee Members: Teresa Wood, Committee Chair/Co-Chair, Edward Joseph Gunther, Committee Chair/Co-Chair, Maricarmen Planas Silva, Committee Member, Michael Verderame, Committee Member, Andrea Manni, Committee Member.

Subjects/Keywords: Insulin-like growth factor receptor; Insulin receptor; Mammary epithelial cells; Quantitative PCR; Insulin-like growth factors; Epidermal growth factor

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Rowzee, A. M. (2008). EXPRESSION AND FUNCTION OF INSULIN-LIKE GROWTH FACTOR SIGNALING RECEPTORS IN MAMMARY EPITHELIAL CELL GROWTH . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7861

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Rowzee, Anne Marie. “EXPRESSION AND FUNCTION OF INSULIN-LIKE GROWTH FACTOR SIGNALING RECEPTORS IN MAMMARY EPITHELIAL CELL GROWTH .” 2008. Thesis, Penn State University. Accessed March 08, 2021. https://submit-etda.libraries.psu.edu/catalog/7861.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Rowzee, Anne Marie. “EXPRESSION AND FUNCTION OF INSULIN-LIKE GROWTH FACTOR SIGNALING RECEPTORS IN MAMMARY EPITHELIAL CELL GROWTH .” 2008. Web. 08 Mar 2021.

Vancouver:

Rowzee AM. EXPRESSION AND FUNCTION OF INSULIN-LIKE GROWTH FACTOR SIGNALING RECEPTORS IN MAMMARY EPITHELIAL CELL GROWTH . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 08]. Available from: https://submit-etda.libraries.psu.edu/catalog/7861.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Rowzee AM. EXPRESSION AND FUNCTION OF INSULIN-LIKE GROWTH FACTOR SIGNALING RECEPTORS IN MAMMARY EPITHELIAL CELL GROWTH . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7861

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


Penn State University

2. Romanelli, Robert John. IGF TYPE I RECEPTOR LOCALIZATION AND TRAFFICKING IN OLIGODENDROCYTE PROGENITOR CELLS: REGULATION OF THE PI-3 KINASE/AKT PATHWAY .

Degree: 2008, Penn State University

Previously we demonstrated that IGF-I mediates long-term survival of oligodendrocyte progenitors (OPs) via sustained phosphorylation and activity of Akt, with concomitant stability and activity of the IGF type-I receptor (IGF-IR). The mechanism by which IGF-I regulates signal transduction, however, is currently undefined. In this dissertation, we investigate the role of IGF-IR trafficking and subcellular localization in sustained Akt phosphorylation in OPs. We report the loss of IGF-IRs from the cell surface, with subsequent recovery during IGF-I stimulation. Using multiple pharmacological inhibitors of receptor trafficking we show that cluster and internalization of the IGF-IR is required to promote Akt phosphorylation and that recycling is required to sustain Akt phosphorylation. We also show that the IGF-IR co-localizes with recycling endosome markers, including the transferrin receptor and rab11, further suggesting a role for IGF-IR recycling. Mathematical analyses predict a model of receptor trafficking consistent with our empirical data of sustained Akt phosphorylation through 120 min. We also report that integrity of cholesterol/glycosphingolipid-enriched membrane microdomains (CEMs), also known as lipid rafts, is required to promote IGF-I mediated Akt phosphorylation. Based on these findings, we propose that the IGF-IR and its signaling proteins are localized within CEMs. Membrane extraction with triton or sodium carbonate yield CEMs from OPs containing the classical rafting proteins caveolin-1 and flotillin-1. Furthermore, the IGF-IR and PI-3K/Akt signaling proteins co-localize in these microdomains We were further interested in determining the role of caveolae, a subset of lipid rafts that contain the protein caveolin-1, in OL biology. We report that caveolin-1 protein expression increased during OL maturation. Additionally, caveolin-1 localization within CEMs correlates with IGF-I stimulation. We also show that the IGF-IR co-localizes with caveolin-1 at a stage of OL maturation when caveolin-1 is maximally expressed, and that the IGF-IR contains a caveolin binding motif that is conserved through evolution. Analysis of brains from caveolin-1 knockout mice reveals aberrant expression of myelin- and OL-specific proteins. The results of this dissertation support our hypothesis that IGF-IR trafficking and localization mediate the sustained phosphorylation of Akt in OPs, and elucidates a role for membrane microdomains in the regulation of IGF-I signaling. Advisors/Committee Members: Teresa Wood, Committee Chair/Co-Chair, Sarah Bronson, Committee Chair/Co-Chair, Steve Levison, Committee Member, Mark Kester, Committee Member, Shao Cong Sun, Committee Chair/Co-Chair.

Subjects/Keywords: oligodendrocytes; Akt; signal transduction; IGF-I; lipid rafts; caveolin; receptor trafficking

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Romanelli, R. J. (2008). IGF TYPE I RECEPTOR LOCALIZATION AND TRAFFICKING IN OLIGODENDROCYTE PROGENITOR CELLS: REGULATION OF THE PI-3 KINASE/AKT PATHWAY . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7191

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Romanelli, Robert John. “IGF TYPE I RECEPTOR LOCALIZATION AND TRAFFICKING IN OLIGODENDROCYTE PROGENITOR CELLS: REGULATION OF THE PI-3 KINASE/AKT PATHWAY .” 2008. Thesis, Penn State University. Accessed March 08, 2021. https://submit-etda.libraries.psu.edu/catalog/7191.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Romanelli, Robert John. “IGF TYPE I RECEPTOR LOCALIZATION AND TRAFFICKING IN OLIGODENDROCYTE PROGENITOR CELLS: REGULATION OF THE PI-3 KINASE/AKT PATHWAY .” 2008. Web. 08 Mar 2021.

Vancouver:

Romanelli RJ. IGF TYPE I RECEPTOR LOCALIZATION AND TRAFFICKING IN OLIGODENDROCYTE PROGENITOR CELLS: REGULATION OF THE PI-3 KINASE/AKT PATHWAY . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 08]. Available from: https://submit-etda.libraries.psu.edu/catalog/7191.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Romanelli RJ. IGF TYPE I RECEPTOR LOCALIZATION AND TRAFFICKING IN OLIGODENDROCYTE PROGENITOR CELLS: REGULATION OF THE PI-3 KINASE/AKT PATHWAY . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7191

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.